FI104631B - Menetelmä uusien 1-asyyli-2-aralkyyli-4-(alkyyli)-aminopiperidiiniyhdisteiden valmistamiseksi - Google Patents
Menetelmä uusien 1-asyyli-2-aralkyyli-4-(alkyyli)-aminopiperidiiniyhdisteiden valmistamiseksi Download PDFInfo
- Publication number
- FI104631B FI104631B FI923575A FI923575A FI104631B FI 104631 B FI104631 B FI 104631B FI 923575 A FI923575 A FI 923575A FI 923575 A FI923575 A FI 923575A FI 104631 B FI104631 B FI 104631B
- Authority
- FI
- Finland
- Prior art keywords
- mmol
- benzyl
- formula
- eller
- piperidinamine
- Prior art date
Links
- 125000000217 alkyl group Chemical group 0.000 title claims abstract description 36
- 238000000034 method Methods 0.000 title claims description 43
- 238000002360 preparation method Methods 0.000 title claims description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 265
- -1 heteroaroyl Chemical group 0.000 claims abstract description 165
- 150000003839 salts Chemical class 0.000 claims abstract description 47
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 26
- 239000001257 hydrogen Substances 0.000 claims abstract description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 22
- 125000001589 carboacyl group Chemical group 0.000 claims abstract description 16
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 15
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 9
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 6
- 239000003814 drug Substances 0.000 claims abstract description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 711
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 687
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 141
- 239000007858 starting material Substances 0.000 claims description 74
- 239000000203 mixture Substances 0.000 claims description 69
- 239000012279 sodium borohydride Substances 0.000 claims description 60
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 60
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 58
- 238000006243 chemical reaction Methods 0.000 claims description 21
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 150000002367 halogens Chemical class 0.000 claims description 19
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 13
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- KLDLRDSRCMJKGM-UHFFFAOYSA-N 3-[chloro-(2-oxo-1,3-oxazolidin-3-yl)phosphoryl]-1,3-oxazolidin-2-one Chemical compound C1COC(=O)N1P(=O)(Cl)N1CCOC1=O KLDLRDSRCMJKGM-UHFFFAOYSA-N 0.000 claims description 11
- 239000003054 catalyst Substances 0.000 claims description 9
- 229910052763 palladium Inorganic materials 0.000 claims description 9
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 8
- 229910000085 borane Inorganic materials 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 6
- 239000007868 Raney catalyst Substances 0.000 claims description 5
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 5
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052783 alkali metal Inorganic materials 0.000 claims description 5
- 239000003086 colorant Substances 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 4
- 239000004305 biphenyl Substances 0.000 claims description 4
- 235000010290 biphenyl Nutrition 0.000 claims description 4
- 238000003776 cleavage reaction Methods 0.000 claims description 4
- 238000005984 hydrogenation reaction Methods 0.000 claims description 4
- 229910052987 metal hydride Inorganic materials 0.000 claims description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
- 229910052697 platinum Inorganic materials 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 3
- 150000001340 alkali metals Chemical class 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000006267 biphenyl group Chemical group 0.000 claims description 3
- 238000009833 condensation Methods 0.000 claims description 3
- 230000005494 condensation Effects 0.000 claims description 3
- 238000004821 distillation Methods 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 3
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- 238000010533 azeotropic distillation Methods 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 150000004681 metal hydrides Chemical class 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 239000012312 sodium hydride Substances 0.000 claims description 2
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims 5
- 241000277284 Salvelinus fontinalis Species 0.000 claims 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims 2
- 239000002002 slurry Substances 0.000 claims 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims 1
- 240000007311 Commiphora myrrha Species 0.000 claims 1
- 235000006965 Commiphora myrrha Nutrition 0.000 claims 1
- 101150079116 MT-CO1 gene Proteins 0.000 claims 1
- 235000007265 Myrrhis odorata Nutrition 0.000 claims 1
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 235000019253 formic acid Nutrition 0.000 claims 1
- 238000009432 framing Methods 0.000 claims 1
- 230000026030 halogenation Effects 0.000 claims 1
- 238000005658 halogenation reaction Methods 0.000 claims 1
- 125000005059 halophenyl group Chemical group 0.000 claims 1
- 229910000462 iron(III) oxide hydroxide Inorganic materials 0.000 claims 1
- 210000005036 nerve Anatomy 0.000 claims 1
- 125000005359 phenoxyalkyl group Chemical group 0.000 claims 1
- DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 claims 1
- 125000003884 phenylalkyl group Chemical group 0.000 claims 1
- QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 abstract description 6
- 102100024304 Protachykinin-1 Human genes 0.000 abstract description 6
- 101800003906 Substance P Proteins 0.000 abstract description 6
- 235000008206 alpha-amino acids Nutrition 0.000 abstract description 3
- 125000003435 aroyl group Chemical group 0.000 abstract description 3
- 125000003710 aryl alkyl group Chemical group 0.000 abstract description 3
- 125000005160 aryl oxy alkyl group Chemical group 0.000 abstract description 3
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 3
- 239000013543 active substance Substances 0.000 abstract description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 3
- 125000003107 substituted aryl group Chemical group 0.000 abstract 2
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 abstract 1
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 abstract 1
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
- 208000035475 disorder Diseases 0.000 abstract 1
- 125000004475 heteroaralkyl group Chemical group 0.000 abstract 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 abstract 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 345
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 243
- 229910021529 ammonia Inorganic materials 0.000 description 171
- 238000000434 field desorption mass spectrometry Methods 0.000 description 158
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 144
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 123
- 239000000243 solution Substances 0.000 description 97
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 75
- 239000006260 foam Substances 0.000 description 72
- 239000003921 oil Substances 0.000 description 71
- 235000019198 oils Nutrition 0.000 description 71
- 235000019439 ethyl acetate Nutrition 0.000 description 61
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 51
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 47
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 46
- 239000000741 silica gel Substances 0.000 description 45
- 229910002027 silica gel Inorganic materials 0.000 description 45
- 239000012074 organic phase Substances 0.000 description 44
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
- 239000011541 reaction mixture Substances 0.000 description 40
- RKOTXQYWCBGZLP-UHFFFAOYSA-N N-[(2,4-difluorophenyl)methyl]-2-ethyl-9-hydroxy-3-methoxy-1,8-dioxospiro[3H-pyrido[1,2-a]pyrazine-4,3'-oxolane]-7-carboxamide Chemical compound CCN1C(OC)C2(CCOC2)N2C=C(C(=O)NCC3=C(F)C=C(F)C=C3)C(=O)C(O)=C2C1=O RKOTXQYWCBGZLP-UHFFFAOYSA-N 0.000 description 38
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 37
- 235000019341 magnesium sulphate Nutrition 0.000 description 37
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 35
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- 239000000460 chlorine Substances 0.000 description 30
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 30
- 239000012267 brine Substances 0.000 description 29
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 26
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 23
- 229910052938 sodium sulfate Inorganic materials 0.000 description 23
- 235000011152 sodium sulphate Nutrition 0.000 description 23
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 20
- 238000003756 stirring Methods 0.000 description 19
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
- 239000002253 acid Substances 0.000 description 17
- 239000012458 free base Substances 0.000 description 17
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 17
- 235000017557 sodium bicarbonate Nutrition 0.000 description 17
- 239000000725 suspension Substances 0.000 description 17
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 16
- GHTFKIFXGCJJCJ-ZWKOTPCHSA-N [(2r,4s)-4-amino-2-benzylpiperidin-1-yl]-(3,5-dichlorophenyl)methanone Chemical compound C([C@H]1N(CC[C@@H](C1)N)C(=O)C=1C=C(Cl)C=C(Cl)C=1)C1=CC=CC=C1 GHTFKIFXGCJJCJ-ZWKOTPCHSA-N 0.000 description 16
- 235000011114 ammonium hydroxide Nutrition 0.000 description 16
- MGCGJBXTNWUHQE-UHFFFAOYSA-N quinoline-4-carbaldehyde Chemical compound C1=CC=C2C(C=O)=CC=NC2=C1 MGCGJBXTNWUHQE-UHFFFAOYSA-N 0.000 description 16
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 14
- 239000013078 crystal Substances 0.000 description 13
- 239000003480 eluent Substances 0.000 description 13
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 229960000583 acetic acid Drugs 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 238000004440 column chromatography Methods 0.000 description 11
- 239000005457 ice water Substances 0.000 description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- DTUQWGWMVIHBKE-UHFFFAOYSA-N phenylacetaldehyde Chemical compound O=CCC1=CC=CC=C1 DTUQWGWMVIHBKE-UHFFFAOYSA-N 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 9
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 239000001632 sodium acetate Substances 0.000 description 8
- 235000017281 sodium acetate Nutrition 0.000 description 8
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 8
- 229940095076 benzaldehyde Drugs 0.000 description 7
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 7
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 150000003840 hydrochlorides Chemical class 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- 239000011230 binding agent Substances 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 239000003085 diluting agent Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000002329 infrared spectrum Methods 0.000 description 5
- 229910052751 metal Inorganic materials 0.000 description 5
- 239000002184 metal Substances 0.000 description 5
- 229940100595 phenylacetaldehyde Drugs 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- SVIRKOCSSOKHBX-UHFFFAOYSA-N 2,2,2-trifluoro-n-piperidin-4-ylacetamide Chemical compound FC(F)(F)C(=O)NC1CCNCC1 SVIRKOCSSOKHBX-UHFFFAOYSA-N 0.000 description 4
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 4
- YQEJEOMPQPBZCR-GFOWMXPYSA-N [(2r)-4-amino-2-benzylpiperidin-1-yl]-(3,5-dimethylphenyl)methanone Chemical compound CC1=CC(C)=CC(C(=O)N2[C@@H](CC(N)CC2)CC=2C=CC=CC=2)=C1 YQEJEOMPQPBZCR-GFOWMXPYSA-N 0.000 description 4
- SVHRYTCAXFKCFS-IZZNHLLZSA-N [(2r,4s)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-(3,5-dichlorophenyl)methanone Chemical compound ClC1=CC(Cl)=CC(C(=O)N2[C@@H](C[C@H](CC2)NCC=2C3=CC=CC=C3N=CC=2)CC=2C=CC=CC=2)=C1 SVHRYTCAXFKCFS-IZZNHLLZSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 238000002285 desorption chemical ionisation mass spectrometry Methods 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 239000003890 substance P antagonist Substances 0.000 description 4
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
- QYBOPMXFDKZJSD-QGZVFWFLSA-N (6r)-1,6-dibenzylpiperidine-2,4-dione Chemical compound C([C@@H]1CC(CC(=O)N1CC=1C=CC=CC=1)=O)C1=CC=CC=C1 QYBOPMXFDKZJSD-QGZVFWFLSA-N 0.000 description 3
- AWNXKZVIZARMME-UHFFFAOYSA-N 1-[[5-[2-[(2-chloropyridin-4-yl)amino]pyrimidin-4-yl]-4-(cyclopropylmethyl)pyrimidin-2-yl]amino]-2-methylpropan-2-ol Chemical compound N=1C(NCC(C)(O)C)=NC=C(C=2N=C(NC=3C=C(Cl)N=CC=3)N=CC=2)C=1CC1CC1 AWNXKZVIZARMME-UHFFFAOYSA-N 0.000 description 3
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 3
- CXKCZFDUOYMOOP-UHFFFAOYSA-N 3,5-dichlorobenzoic acid Chemical compound OC(=O)C1=CC(Cl)=CC(Cl)=C1 CXKCZFDUOYMOOP-UHFFFAOYSA-N 0.000 description 3
- ZJIOBDJEKDUUCI-UHFFFAOYSA-N 3,5-dimethylbenzoyl chloride Chemical compound CC1=CC(C)=CC(C(Cl)=O)=C1 ZJIOBDJEKDUUCI-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 3
- 150000003863 ammonium salts Chemical class 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 3
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 3
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 3
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
- VNSPYXJVJXNHJG-YIKNKFAXSA-N (2R)-2-amino-1-[(2R,4S)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-3-phenylpropan-1-one Chemical compound C([C@@H](N)C(=O)N1[C@@H](C[C@H](CC1)NCC=1C2=CC=CC=C2N=CC=1)CC=1C=CC=CC=1)C1=CC=CC=C1 VNSPYXJVJXNHJG-YIKNKFAXSA-N 0.000 description 2
- VNSPYXJVJXNHJG-GKRYNVPLSA-N (2S)-2-amino-1-[(2R,4S)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-3-phenylpropan-1-one Chemical compound C([C@H](N)C(=O)N1[C@@H](C[C@H](CC1)NCC=1C2=CC=CC=C2N=CC=1)CC=1C=CC=CC=1)C1=CC=CC=C1 VNSPYXJVJXNHJG-GKRYNVPLSA-N 0.000 description 2
- QYQVWXSKXOUUNG-GMUIIQOCSA-N (2r)-1,2-dibenzylpiperidin-4-one;ethene Chemical group C=C.C([C@H]1CC=2C=CC=CC=2)C(=O)CCN1CC1=CC=CC=C1 QYQVWXSKXOUUNG-GMUIIQOCSA-N 0.000 description 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 2
- LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 2
- 125000001088 1-naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- PKZJLOCLABXVMC-UHFFFAOYSA-N 2-Methoxybenzaldehyde Chemical compound COC1=CC=CC=C1C=O PKZJLOCLABXVMC-UHFFFAOYSA-N 0.000 description 2
- UOBYKYZJUGYBDK-UHFFFAOYSA-N 2-naphthoic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CC=C21 UOBYKYZJUGYBDK-UHFFFAOYSA-N 0.000 description 2
- VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 2
- HVFQJWGYVXKLTE-UHFFFAOYSA-N 3,5-bis(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 HVFQJWGYVXKLTE-UHFFFAOYSA-N 0.000 description 2
- GGHLXLVPNZMBQR-UHFFFAOYSA-N 3,5-dichlorobenzoyl chloride Chemical compound ClC(=O)C1=CC(Cl)=CC(Cl)=C1 GGHLXLVPNZMBQR-UHFFFAOYSA-N 0.000 description 2
- UYEMGAFJOZZIFP-UHFFFAOYSA-N 3,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC(O)=C1 UYEMGAFJOZZIFP-UHFFFAOYSA-N 0.000 description 2
- IWPZKOJSYQZABD-UHFFFAOYSA-N 3,5-dimethoxybenzoic acid Chemical compound COC1=CC(OC)=CC(C(O)=O)=C1 IWPZKOJSYQZABD-UHFFFAOYSA-N 0.000 description 2
- XHQZJYCNDZAGLW-UHFFFAOYSA-N 3-methoxybenzoic acid Chemical compound COC1=CC=CC(C(O)=O)=C1 XHQZJYCNDZAGLW-UHFFFAOYSA-N 0.000 description 2
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 2
- ZEYHEAKUIGZSGI-UHFFFAOYSA-N 4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1 ZEYHEAKUIGZSGI-UHFFFAOYSA-N 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 2
- QPXROMJDFPQBAT-IZZNHLLZSA-N [(2r,4s)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-[3,5-bis(trifluoromethyl)phenyl]methanone Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C(=O)N2[C@@H](C[C@H](CC2)NCC=2C3=CC=CC=C3N=CC=2)CC=2C=CC=CC=2)=C1 QPXROMJDFPQBAT-IZZNHLLZSA-N 0.000 description 2
- CZEMMCCUTSUYFU-ZWKOTPCHSA-N [(2r,4s)-4-amino-2-benzylpiperidin-1-yl]-[3,5-bis(trifluoromethyl)phenyl]methanone Chemical compound C([C@H]1N(CC[C@@H](C1)N)C(=O)C=1C=C(C=C(C=1)C(F)(F)F)C(F)(F)F)C1=CC=CC=C1 CZEMMCCUTSUYFU-ZWKOTPCHSA-N 0.000 description 2
- YQEJEOMPQPBZCR-ANYOKISRSA-N [(2s)-4-amino-2-benzylpiperidin-1-yl]-(3,5-dimethylphenyl)methanone Chemical compound CC1=CC(C)=CC(C(=O)N2[C@H](CC(N)CC2)CC=2C=CC=CC=2)=C1 YQEJEOMPQPBZCR-ANYOKISRSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 150000001371 alpha-amino acids Chemical class 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- CPPWUCAZPYCXLB-UHFFFAOYSA-N benzyl 2-benzyl-4-oxo-2,3-dihydropyridine-1-carboxylate Chemical compound C1=CC(=O)CC(CC=2C=CC=CC=2)N1C(=O)OCC1=CC=CC=C1 CPPWUCAZPYCXLB-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 208000015114 central nervous system disease Diseases 0.000 description 2
- 238000000262 chemical ionisation mass spectrometry Methods 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000013401 experimental design Methods 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 2
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 2
- OLNJUISKUQQNIM-UHFFFAOYSA-N indole-3-carbaldehyde Chemical compound C1=CC=C2C(C=O)=CNC2=C1 OLNJUISKUQQNIM-UHFFFAOYSA-N 0.000 description 2
- KMAKOBLIOCQGJP-UHFFFAOYSA-N indole-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CNC2=C1 KMAKOBLIOCQGJP-UHFFFAOYSA-N 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 2
- 125000005647 linker group Chemical group 0.000 description 2
- GUWHRJQTTVADPB-UHFFFAOYSA-N lithium azide Chemical compound [Li+].[N-]=[N+]=[N-] GUWHRJQTTVADPB-UHFFFAOYSA-N 0.000 description 2
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- VTYBFJARUKACCW-DUSLRRAJSA-N methyl (6r)-1,6-dibenzyl-2,4-dioxopiperidine-3-carboxylate Chemical compound C([C@@H]1CC(=O)C(C(N1CC=1C=CC=CC=1)=O)C(=O)OC)C1=CC=CC=C1 VTYBFJARUKACCW-DUSLRRAJSA-N 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- SVZJUQMWWXRFTJ-ALGPSANZSA-N n-[(2r)-2-benzylpiperidin-4-yl]-2,2,2-trifluoroacetamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1C(NC(=O)C(F)(F)F)CCN[C@@H]1CC1=CC=CC=C1 SVZJUQMWWXRFTJ-ALGPSANZSA-N 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- BCIIMDOZSUCSEN-UHFFFAOYSA-N piperidin-4-amine Chemical compound NC1CCNCC1 BCIIMDOZSUCSEN-UHFFFAOYSA-N 0.000 description 2
- 238000004987 plasma desorption mass spectroscopy Methods 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- VQMSRUREDGBWKT-UHFFFAOYSA-N quinoline-4-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=NC2=C1 VQMSRUREDGBWKT-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- GHLJYHXYFFNJTP-UHFFFAOYSA-N tert-butyl 6-benzyl-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC=CC1CC1=CC=CC=C1 GHLJYHXYFFNJTP-UHFFFAOYSA-N 0.000 description 2
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 2
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical compound C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 description 1
- REPVLJRCJUVQFA-UHFFFAOYSA-N (-)-isopinocampheol Natural products C1C(O)C(C)C2C(C)(C)C1C2 REPVLJRCJUVQFA-UHFFFAOYSA-N 0.000 description 1
- PJDOVGDUMXUTHB-IZZNHLLZSA-N (2R,4S)-2-benzyl-1-[(2,4-dichlorophenyl)methyl]-N-(quinolin-4-ylmethyl)piperidin-4-amine Chemical compound ClC1=CC(Cl)=CC=C1CN1[C@H](CC=2C=CC=CC=2)C[C@@H](NCC=2C3=CC=CC=C3N=CC=2)CC1 PJDOVGDUMXUTHB-IZZNHLLZSA-N 0.000 description 1
- UHGAIKIGXLTYFM-IZZNHLLZSA-N (2R,4S)-2-benzyl-N-phenyl-4-(quinolin-4-ylmethylamino)piperidine-1-carboxamide Chemical compound N1([C@@H](C[C@H](CC1)NCC=1C2=CC=CC=C2N=CC=1)CC=1C=CC=CC=1)C(=O)NC1=CC=CC=C1 UHGAIKIGXLTYFM-IZZNHLLZSA-N 0.000 description 1
- MWDZFZWEWVTSFC-HXUWFJFHSA-N (2r)-1,2-dibenzyl-n-methoxypiperidin-4-imine Chemical compound C([C@H]1CC=2C=CC=CC=2)C(=NOC)CCN1CC1=CC=CC=C1 MWDZFZWEWVTSFC-HXUWFJFHSA-N 0.000 description 1
- WOKPOVXJHMRHOH-MUMRKEEXSA-N (2r)-1,2-dibenzylpiperidin-4-amine Chemical compound C([C@H]1CC=2C=CC=CC=2)C(N)CCN1CC1=CC=CC=C1 WOKPOVXJHMRHOH-MUMRKEEXSA-N 0.000 description 1
- QVAKMEJNSFNIMY-GOSISDBHSA-N (2r)-1,2-dibenzylpiperidin-4-one Chemical compound C([C@H]1CC=2C=CC=CC=2)C(=O)CCN1CC1=CC=CC=C1 QVAKMEJNSFNIMY-GOSISDBHSA-N 0.000 description 1
- KCHZSHRRZWMRFQ-RRPNLBNLSA-N (2r,4s)-2-benzyl-1-[[3,5-bis(trifluoromethyl)phenyl]methyl]-n-(quinolin-4-ylmethyl)piperidin-4-amine Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(CN2[C@@H](C[C@H](CC2)NCC=2C3=CC=CC=C3N=CC=2)CC=2C=CC=CC=2)=C1 KCHZSHRRZWMRFQ-RRPNLBNLSA-N 0.000 description 1
- GHTFKIFXGCJJCJ-UHFFFAOYSA-N (4-amino-2-benzylpiperidin-1-yl)-(3,5-dichlorophenyl)methanone Chemical compound C1C(N)CCN(C(=O)C=2C=C(Cl)C=C(Cl)C=2)C1CC1=CC=CC=C1 GHTFKIFXGCJJCJ-UHFFFAOYSA-N 0.000 description 1
- VOJVHQYMNKZMCL-LJQANCHMSA-N (6R)-1,6-dibenzyl-4-methoxyiminopiperidin-2-one Chemical compound C([C@@H]1CC(CC(=O)N1CC=1C=CC=CC=1)=NOC)C1=CC=CC=C1 VOJVHQYMNKZMCL-LJQANCHMSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 1
- MIOPJNTWMNEORI-XVKPBYJWSA-N (R)-camphorsulfonic acid Chemical compound C1C[C@]2(CS(O)(=O)=O)C(=O)C[C@H]1C2(C)C MIOPJNTWMNEORI-XVKPBYJWSA-N 0.000 description 1
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- IWYDHOAUDWTVEP-ZETCQYMHSA-N (S)-mandelic acid Chemical compound OC(=O)[C@@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-ZETCQYMHSA-N 0.000 description 1
- 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 description 1
- KPKNTUUIEVXMOH-UHFFFAOYSA-N 1,4-dioxa-8-azaspiro[4.5]decane Chemical compound O1CCOC11CCNCC1 KPKNTUUIEVXMOH-UHFFFAOYSA-N 0.000 description 1
- ATLQGZVLWOURFU-UHFFFAOYSA-N 1-(bromomethyl)-3,5-bis(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC(CBr)=CC(C(F)(F)F)=C1 ATLQGZVLWOURFU-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- LOTWWUVKEYBZNQ-AJQTZOPKSA-N 1-[(2R,4S)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-2,2-diphenylethanone Chemical compound N1([C@@H](C[C@H](CC1)NCC=1C2=CC=CC=C2N=CC=1)CC=1C=CC=CC=1)C(=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 LOTWWUVKEYBZNQ-AJQTZOPKSA-N 0.000 description 1
- UNGLLXYYFQWJQO-RRPNLBNLSA-N 1-[(2R,4S)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-2-(4-chlorophenyl)ethanone Chemical compound C1=CC(Cl)=CC=C1CC(=O)N1[C@H](CC=2C=CC=CC=2)C[C@@H](NCC=2C3=CC=CC=C3N=CC=2)CC1 UNGLLXYYFQWJQO-RRPNLBNLSA-N 0.000 description 1
- YTSROYMDXZJDOO-IOWSJCHKSA-N 1-[(2R,4S)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-2-naphthalen-2-ylethanone Chemical compound C([C@@H]1C[C@H](CCN1C(CC=1C=C2C=CC=CC2=CC=1)=O)NCC=1C2=CC=CC=C2N=CC=1)C1=CC=CC=C1 YTSROYMDXZJDOO-IOWSJCHKSA-N 0.000 description 1
- QEDDFVHLAFIWMP-IZZNHLLZSA-N 1-[(2R,4S)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-2-pyridin-2-ylethanone Chemical compound N1([C@@H](C[C@H](CC1)NCC=1C2=CC=CC=C2N=CC=1)CC=1C=CC=CC=1)C(=O)CC1=CC=CC=N1 QEDDFVHLAFIWMP-IZZNHLLZSA-N 0.000 description 1
- HVFGGKAAGSRBLP-IZZNHLLZSA-N 1-[(2R,4S)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-2-pyridin-4-ylethanone Chemical compound N1([C@@H](C[C@H](CC1)NCC=1C2=CC=CC=C2N=CC=1)CC=1C=CC=CC=1)C(=O)CC1=CC=NC=C1 HVFGGKAAGSRBLP-IZZNHLLZSA-N 0.000 description 1
- YNHDEHNAJAUKAK-BJKOFHAPSA-N 1-[(2r,4s)-2-benzyl-1-(3,5-dichlorobenzoyl)piperidin-4-yl]-3-phenylurea Chemical compound ClC1=CC(Cl)=CC(C(=O)N2[C@@H](C[C@H](CC2)NC(=O)NC=2C=CC=CC=2)CC=2C=CC=CC=2)=C1 YNHDEHNAJAUKAK-BJKOFHAPSA-N 0.000 description 1
- NKOIXVRNECOYPP-RRPNLBNLSA-N 1-[(2r,4s)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-2-phenylethanone Chemical compound N1([C@@H](C[C@H](CC1)NCC=1C2=CC=CC=C2N=CC=1)CC=1C=CC=CC=1)C(=O)CC1=CC=CC=C1 NKOIXVRNECOYPP-RRPNLBNLSA-N 0.000 description 1
- SZYDAXTZLNIAOQ-UHFFFAOYSA-N 1-[2-(2-bromoethoxy)-4-chlorophenyl]-1,2,4-triazole Chemical compound BrCCOC1=CC(Cl)=CC=C1N1N=CN=C1 SZYDAXTZLNIAOQ-UHFFFAOYSA-N 0.000 description 1
- LCJLFGSKHBDOAY-UHFFFAOYSA-N 1-acetylindole-3-carboxaldehyde Chemical compound C1=CC=C2N(C(=O)C)C=C(C=O)C2=C1 LCJLFGSKHBDOAY-UHFFFAOYSA-N 0.000 description 1
- GQIRIWDEZSKOCN-UHFFFAOYSA-N 1-chloro-n,n,2-trimethylprop-1-en-1-amine Chemical compound CN(C)C(Cl)=C(C)C GQIRIWDEZSKOCN-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- WGUXTQDCAZNJIF-UHFFFAOYSA-N 1-methyl-3,5-bis(trifluoromethyl)benzene Chemical group CC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 WGUXTQDCAZNJIF-UHFFFAOYSA-N 0.000 description 1
- SQAINHDHICKHLX-UHFFFAOYSA-N 1-naphthaldehyde Chemical compound C1=CC=C2C(C=O)=CC=CC2=C1 SQAINHDHICKHLX-UHFFFAOYSA-N 0.000 description 1
- HLLGFGBLKOIZOM-UHFFFAOYSA-N 2,2-diphenylacetaldehyde Chemical compound C=1C=CC=CC=1C(C=O)C1=CC=CC=C1 HLLGFGBLKOIZOM-UHFFFAOYSA-N 0.000 description 1
- 125000000579 2,2-diphenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(C1=C([H])C([H])=C([H])C([H])=C1[H])C([H])([H])* 0.000 description 1
- CEOCVKWBUWKBKA-UHFFFAOYSA-N 2,4-dichlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C=C1Cl CEOCVKWBUWKBKA-UHFFFAOYSA-N 0.000 description 1
- JBLIDPPHFGWTKU-UHFFFAOYSA-N 2,6-dichlorobenzoyl chloride Chemical compound ClC(=O)C1=C(Cl)C=CC=C1Cl JBLIDPPHFGWTKU-UHFFFAOYSA-N 0.000 description 1
- 125000004098 2,6-dichlorobenzoyl group Chemical group O=C([*])C1=C(Cl)C([H])=C([H])C([H])=C1Cl 0.000 description 1
- ADDZHRRCUWNSCS-UHFFFAOYSA-N 2-Benzofurancarboxaldehyde Chemical compound C1=CC=C2OC(C=O)=CC2=C1 ADDZHRRCUWNSCS-UHFFFAOYSA-N 0.000 description 1
- IKCLCGXPQILATA-UHFFFAOYSA-N 2-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1Cl IKCLCGXPQILATA-UHFFFAOYSA-N 0.000 description 1
- WBJWXIQDBDZMAW-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carbonyl chloride Chemical compound C1=CC=CC2=C(C(Cl)=O)C(O)=CC=C21 WBJWXIQDBDZMAW-UHFFFAOYSA-N 0.000 description 1
- VIBOGIYPPWLDTI-UHFFFAOYSA-N 2-naphthylacetic acid Chemical compound C1=CC=CC2=CC(CC(=O)O)=CC=C21 VIBOGIYPPWLDTI-UHFFFAOYSA-N 0.000 description 1
- WKJRYVOTVRPAFN-UHFFFAOYSA-N 2-pyridin-1-ium-4-ylacetic acid;chloride Chemical compound Cl.OC(=O)CC1=CC=NC=C1 WKJRYVOTVRPAFN-UHFFFAOYSA-N 0.000 description 1
- MQVISALTZUNQSK-UHFFFAOYSA-N 2-pyridin-2-ylacetic acid;hydrochloride Chemical compound Cl.OC(=O)CC1=CC=CC=N1 MQVISALTZUNQSK-UHFFFAOYSA-N 0.000 description 1
- ZWUSBSHBFFPRNE-UHFFFAOYSA-N 3,4-dichlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1Cl ZWUSBSHBFFPRNE-UHFFFAOYSA-N 0.000 description 1
- 125000006512 3,4-dichlorobenzyl group Chemical group [H]C1=C(Cl)C(Cl)=C([H])C(=C1[H])C([H])([H])* 0.000 description 1
- SFLFCQJQOIZMHF-UHFFFAOYSA-N 3,4-dihydro-2h-chromene-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)CCC2=C1 SFLFCQJQOIZMHF-UHFFFAOYSA-N 0.000 description 1
- SFTFNJZWZHASAQ-UHFFFAOYSA-N 3,5-dibromobenzoic acid Chemical compound OC(=O)C1=CC(Br)=CC(Br)=C1 SFTFNJZWZHASAQ-UHFFFAOYSA-N 0.000 description 1
- UMVOQQDNEYOJOK-UHFFFAOYSA-N 3,5-dimethylbenzoic acid Chemical compound CC1=CC(C)=CC(C(O)=O)=C1 UMVOQQDNEYOJOK-UHFFFAOYSA-N 0.000 description 1
- NEGFNJRAUMCZMY-UHFFFAOYSA-N 3-(dimethylamino)benzoic acid Chemical compound CN(C)C1=CC=CC(C(O)=O)=C1 NEGFNJRAUMCZMY-UHFFFAOYSA-N 0.000 description 1
- JFAJYVSYQOAFMX-RRPNLBNLSA-N 3-[(2R,4S)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidine-1-carbonyl]benzonitrile Chemical compound C([C@@H]1C[C@H](CCN1C(=O)C=1C=C(C=CC=1)C#N)NCC=1C2=CC=CC=C2N=CC=1)C1=CC=CC=C1 JFAJYVSYQOAFMX-RRPNLBNLSA-N 0.000 description 1
- VOIZNVUXCQLQHS-UHFFFAOYSA-N 3-bromobenzoic acid Chemical compound OC(=O)C1=CC=CC(Br)=C1 VOIZNVUXCQLQHS-UHFFFAOYSA-N 0.000 description 1
- WHIHIKVIWVIIER-UHFFFAOYSA-N 3-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(Cl)=C1 WHIHIKVIWVIIER-UHFFFAOYSA-N 0.000 description 1
- GYLKKXHEIIFTJH-UHFFFAOYSA-N 3-cyanobenzoic acid Chemical compound OC(=O)C1=CC=CC(C#N)=C1 GYLKKXHEIIFTJH-UHFFFAOYSA-N 0.000 description 1
- PQOCJONTQYLEFC-UHFFFAOYSA-N 3-methoxy-3-oxopropanoic acid;hydrochloride Chemical compound Cl.COC(=O)CC(O)=O PQOCJONTQYLEFC-UHFFFAOYSA-N 0.000 description 1
- DRZGHNXLEQHVHB-UHFFFAOYSA-N 3-methyl-1-benzothiophene-2-carbaldehyde Chemical compound C1=CC=C2C(C)=C(C=O)SC2=C1 DRZGHNXLEQHVHB-UHFFFAOYSA-N 0.000 description 1
- FQXQBFUUVCDIRK-UHFFFAOYSA-N 3-trifluoromethylbenzoic acid Chemical compound OC(=O)C1=CC=CC(C(F)(F)F)=C1 FQXQBFUUVCDIRK-UHFFFAOYSA-N 0.000 description 1
- SNKAAIQBOBROQQ-UHFFFAOYSA-N 4,7-dimethylbicyclo[2.2.1]heptane-7-carbonyl chloride Chemical compound C1CC2CCC1(C)C2(C)C(Cl)=O SNKAAIQBOBROQQ-UHFFFAOYSA-N 0.000 description 1
- 125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 description 1
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 1
- XRHGYUZYPHTUJZ-UHFFFAOYSA-N 4-chlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1 XRHGYUZYPHTUJZ-UHFFFAOYSA-N 0.000 description 1
- CDPKJZJVTHSESZ-UHFFFAOYSA-N 4-chlorophenylacetic acid Chemical compound OC(=O)CC1=CC=C(Cl)C=C1 CDPKJZJVTHSESZ-UHFFFAOYSA-N 0.000 description 1
- MBVFRSJFKMJRHA-UHFFFAOYSA-N 4-fluoro-1-benzofuran-7-carbaldehyde Chemical compound FC1=CC=C(C=O)C2=C1C=CO2 MBVFRSJFKMJRHA-UHFFFAOYSA-N 0.000 description 1
- OURXRFYZEOUCRM-UHFFFAOYSA-N 4-hydroxymorpholine Chemical compound ON1CCOCC1 OURXRFYZEOUCRM-UHFFFAOYSA-N 0.000 description 1
- XQABVLBGNWBWIV-UHFFFAOYSA-N 4-methoxypyridine Chemical compound COC1=CC=NC=C1 XQABVLBGNWBWIV-UHFFFAOYSA-N 0.000 description 1
- YEBJVSLNUMZXRJ-UHFFFAOYSA-N 5-methoxyindole-2-carboxylic acid Chemical compound COC1=CC=C2NC(C(O)=O)=CC2=C1 YEBJVSLNUMZXRJ-UHFFFAOYSA-N 0.000 description 1
- TUWARWGEOHQXCO-UHFFFAOYSA-N 5-methoxyindole-3-carbaldehyde Chemical compound COC1=CC=C2NC=C(C=O)C2=C1 TUWARWGEOHQXCO-UHFFFAOYSA-N 0.000 description 1
- PBXYLMVLLSYZLN-UHFFFAOYSA-N 5beta-Ranol Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)CCO)C)C1(C)C(O)C2 PBXYLMVLLSYZLN-UHFFFAOYSA-N 0.000 description 1
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- AHCDKANCCBEQJJ-UHFFFAOYSA-N 9-bromo-9h-fluorene Chemical compound C1=CC=C2C(Br)C3=CC=CC=C3C2=C1 AHCDKANCCBEQJJ-UHFFFAOYSA-N 0.000 description 1
- DNVJGJUGFFYUPT-UHFFFAOYSA-N 9h-fluorene-9-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)C3=CC=CC=C3C2=C1 DNVJGJUGFFYUPT-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 208000009079 Bronchial Spasm Diseases 0.000 description 1
- 208000014181 Bronchial disease Diseases 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- 206010006482 Bronchospasm Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- OFVBLKINTLPEGH-UHFFFAOYSA-N DL-beta-Homophenylalanine Chemical compound OC(=O)CC(N)CC1=CC=CC=C1 OFVBLKINTLPEGH-UHFFFAOYSA-N 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 241000699694 Gerbillinae Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- OWIKHYCFFJSOEH-UHFFFAOYSA-N Isocyanic acid Chemical compound N=C=O OWIKHYCFFJSOEH-UHFFFAOYSA-N 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- STVVMTBJNDTZBF-VIFPVBQESA-N L-phenylalaninol Chemical compound OC[C@@H](N)CC1=CC=CC=C1 STVVMTBJNDTZBF-VIFPVBQESA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 208000019430 Motor disease Diseases 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- JKMDRPCTBYYGDB-UHFFFAOYSA-N N-(1-benzylpiperidin-4-yl)-2,2,2-trifluoro-N-(quinolin-4-ylmethyl)acetamide Chemical compound C(C1=CC=CC=C1)N1CCC(CC1)N(C(C(F)(F)F)=O)CC1=CC=NC2=CC=CC=C12 JKMDRPCTBYYGDB-UHFFFAOYSA-N 0.000 description 1
- NMPYARZUFZMXCQ-BJKOFHAPSA-N N-[(2R,4S)-2-benzyl-1-(3,5-dichlorobenzoyl)piperidin-4-yl]-1H-indole-2-carboxamide Chemical compound ClC1=CC(Cl)=CC(C(=O)N2[C@@H](C[C@H](CC2)NC(=O)C=2NC3=CC=CC=C3C=2)CC=2C=CC=CC=2)=C1 NMPYARZUFZMXCQ-BJKOFHAPSA-N 0.000 description 1
- VQUMPBVNOGTKDC-XZOQPEGZSA-N N-[(2R,4S)-2-benzyl-1-(3,5-dichlorobenzoyl)piperidin-4-yl]-1H-indole-3-carboxamide Chemical compound ClC1=CC(Cl)=CC(C(=O)N2[C@@H](C[C@H](CC2)NC(=O)C=2C3=CC=CC=C3NC=2)CC=2C=CC=CC=2)=C1 VQUMPBVNOGTKDC-XZOQPEGZSA-N 0.000 description 1
- ZHRSSOQMKIDFLJ-IZZNHLLZSA-N N-[(2R,4S)-2-benzyl-1-(3,5-dichlorobenzoyl)piperidin-4-yl]naphthalene-1-carboxamide Chemical compound ClC1=CC(Cl)=CC(C(=O)N2[C@@H](C[C@H](CC2)NC(=O)C=2C3=CC=CC=C3C=CC=2)CC=2C=CC=CC=2)=C1 ZHRSSOQMKIDFLJ-IZZNHLLZSA-N 0.000 description 1
- TXNNPLICSWXEJH-WUFINQPMSA-N N-[(2R,4S)-2-benzyl-1-(3,5-dichlorobenzoyl)piperidin-4-yl]naphthalene-2-carboxamide Chemical compound ClC1=CC(Cl)=CC(C(=O)N2[C@@H](C[C@H](CC2)NC(=O)C=2C=C3C=CC=CC3=CC=2)CC=2C=CC=CC=2)=C1 TXNNPLICSWXEJH-WUFINQPMSA-N 0.000 description 1
- FNVUVPNQTFHBKE-LBRLCBGXSA-N N-[(2S)-1-[(2R,4S)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-1-oxo-3-phenylpropan-2-yl]acetamide Chemical compound C([C@H](NC(=O)C)C(=O)N1[C@@H](C[C@H](CC1)NCC=1C2=CC=CC=C2N=CC=1)CC=1C=CC=CC=1)C1=CC=CC=C1 FNVUVPNQTFHBKE-LBRLCBGXSA-N 0.000 description 1
- WYZFINSLXAEFDT-UHFFFAOYSA-N N-but-3-enoxy-2-phenylacetamide Chemical compound C(CC=C)ONC(=O)CC1=CC=CC=C1 WYZFINSLXAEFDT-UHFFFAOYSA-N 0.000 description 1
- 102000003797 Neuropeptides Human genes 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 102000003141 Tachykinin Human genes 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- HSSZIZURYDLFBR-IZZNHLLZSA-N [(2R,4S)-2-benzyl-4-(2-phenylethylamino)piperidin-1-yl]-(3,5-dichlorophenyl)methanone Chemical compound ClC1=CC(Cl)=CC(C(=O)N2[C@@H](C[C@H](CC2)NCCC=2C=CC=CC=2)CC=2C=CC=CC=2)=C1 HSSZIZURYDLFBR-IZZNHLLZSA-N 0.000 description 1
- GMRGTANIXBAITC-BJKOFHAPSA-N [(2R,4S)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-(2,4-dichlorophenyl)methanone Chemical compound ClC1=CC(Cl)=CC=C1C(=O)N1[C@H](CC=2C=CC=CC=2)C[C@@H](NCC=2C3=CC=CC=C3N=CC=2)CC1 GMRGTANIXBAITC-BJKOFHAPSA-N 0.000 description 1
- OLBLVUWSLMGMAC-XZOQPEGZSA-N [(2R,4S)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-(2,6-dichlorophenyl)methanone Chemical compound ClC1=CC=CC(Cl)=C1C(=O)N1[C@H](CC=2C=CC=CC=2)C[C@@H](NCC=2C3=CC=CC=C3N=CC=2)CC1 OLBLVUWSLMGMAC-XZOQPEGZSA-N 0.000 description 1
- SWJQLKFMMMKPTM-IZZNHLLZSA-N [(2R,4S)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-(3-bromophenyl)methanone Chemical compound BrC1=CC=CC(C(=O)N2[C@@H](C[C@H](CC2)NCC=2C3=CC=CC=C3N=CC=2)CC=2C=CC=CC=2)=C1 SWJQLKFMMMKPTM-IZZNHLLZSA-N 0.000 description 1
- JPXVHUSUJOPPRO-IZZNHLLZSA-N [(2R,4S)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-(3-methoxyphenyl)methanone Chemical compound COC1=CC=CC(C(=O)N2[C@@H](C[C@H](CC2)NCC=2C3=CC=CC=C3N=CC=2)CC=2C=CC=CC=2)=C1 JPXVHUSUJOPPRO-IZZNHLLZSA-N 0.000 description 1
- LEUPFBCFTGVXOL-RRPNLBNLSA-N [(2R,4S)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-(3-methylphenyl)methanone Chemical compound CC1=CC=CC(C(=O)N2[C@@H](C[C@H](CC2)NCC=2C3=CC=CC=C3N=CC=2)CC=2C=CC=CC=2)=C1 LEUPFBCFTGVXOL-RRPNLBNLSA-N 0.000 description 1
- ASEDEWHDENIPDD-WUFINQPMSA-N [(2R,4S)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-(9H-fluoren-9-yl)methanone Chemical compound C([C@@H]1C[C@H](CCN1C(C1C2=CC=CC=C2C2=CC=CC=C21)=O)NCC=1C2=CC=CC=C2N=CC=1)C1=CC=CC=C1 ASEDEWHDENIPDD-WUFINQPMSA-N 0.000 description 1
- IRIPLYWEVUUMMR-IZZNHLLZSA-N [(2R,4S)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-[3-(trifluoromethyl)phenyl]methanone Chemical compound FC(F)(F)C1=CC=CC(C(=O)N2[C@@H](C[C@H](CC2)NCC=2C3=CC=CC=C3N=CC=2)CC=2C=CC=CC=2)=C1 IRIPLYWEVUUMMR-IZZNHLLZSA-N 0.000 description 1
- CXAMYWCVLTUBSH-RRPNLBNLSA-N [(2R,4S)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-quinolin-2-ylmethanone Chemical compound C([C@@H]1C[C@H](CCN1C(=O)C=1N=C2C=CC=CC2=CC=1)NCC=1C2=CC=CC=C2N=CC=1)C1=CC=CC=C1 CXAMYWCVLTUBSH-RRPNLBNLSA-N 0.000 description 1
- YKVYHVHNCZRXFP-LOSJGSFVSA-N [(2R,4S)-2-benzyl-4-[(2-methoxyphenyl)methylamino]piperidin-1-yl]-(3,5-dichlorophenyl)methanone Chemical compound COC1=CC=CC=C1CN[C@@H]1C[C@@H](CC=2C=CC=CC=2)N(C(=O)C=2C=C(Cl)C=C(Cl)C=2)CC1 YKVYHVHNCZRXFP-LOSJGSFVSA-N 0.000 description 1
- MGZFVRUXZAEKNI-XZWHSSHBSA-N [(2R,4S)-4-(benzhydrylamino)-2-benzylpiperidin-1-yl]-(3,5-dichlorophenyl)methanone Chemical compound ClC1=CC(Cl)=CC(C(=O)N2[C@@H](C[C@H](CC2)NC(C=2C=CC=CC=2)C=2C=CC=CC=2)CC=2C=CC=CC=2)=C1 MGZFVRUXZAEKNI-XZWHSSHBSA-N 0.000 description 1
- BOGOWHBQGVNLOS-LTRMXRMOSA-N [(2r,4r)-2-benzyl-4-(2-phenylethylamino)piperidin-1-yl]-(3,5-dimethylphenyl)methanone;hydrochloride Chemical compound Cl.CC1=CC(C)=CC(C(=O)N2[C@@H](C[C@@H](CC2)NCCC=2C=CC=CC=2)CC=2C=CC=CC=2)=C1 BOGOWHBQGVNLOS-LTRMXRMOSA-N 0.000 description 1
- DXZSWPUGPSLERD-CXOSUTOZSA-N [(2r,4r)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-(3,5-dimethylphenyl)methanone;dihydrochloride Chemical compound Cl.Cl.CC1=CC(C)=CC(C(=O)N2[C@@H](C[C@@H](CC2)NCC=2C3=CC=CC=C3N=CC=2)CC=2C=CC=CC=2)=C1 DXZSWPUGPSLERD-CXOSUTOZSA-N 0.000 description 1
- ZMPABVVPVGDMMD-WUFINQPMSA-N [(2r,4s)-2-[(4-chlorophenyl)methyl]-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-(3,5-dimethylphenyl)methanone Chemical compound CC1=CC(C)=CC(C(=O)N2[C@@H](C[C@H](CC2)NCC=2C3=CC=CC=C3N=CC=2)CC=2C=CC(Cl)=CC=2)=C1 ZMPABVVPVGDMMD-WUFINQPMSA-N 0.000 description 1
- UISKGTZVONGFBF-URLMMPGGSA-N [(2r,4s)-2-benzyl-4-(quinolin-3-ylmethylamino)piperidin-1-yl]-(3,5-dimethylphenyl)methanone Chemical compound CC1=CC(C)=CC(C(=O)N2[C@@H](C[C@H](CC2)NCC=2C=C3C=CC=CC3=NC=2)CC=2C=CC=CC=2)=C1 UISKGTZVONGFBF-URLMMPGGSA-N 0.000 description 1
- BFTNGPWIAXYGDV-BJKOFHAPSA-N [(2r,4s)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-(2-chlorophenyl)methanone Chemical compound ClC1=CC=CC=C1C(=O)N1[C@H](CC=2C=CC=CC=2)C[C@@H](NCC=2C3=CC=CC=C3N=CC=2)CC1 BFTNGPWIAXYGDV-BJKOFHAPSA-N 0.000 description 1
- RDQXAZMERWVFCE-IZZNHLLZSA-N [(2r,4s)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-(3,5-dibromophenyl)methanone Chemical compound BrC1=CC(Br)=CC(C(=O)N2[C@@H](C[C@H](CC2)NCC=2C3=CC=CC=C3N=CC=2)CC=2C=CC=CC=2)=C1 RDQXAZMERWVFCE-IZZNHLLZSA-N 0.000 description 1
- DOXKBIISJMVOAL-BJKOFHAPSA-N [(2r,4s)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-(3,5-dihydroxyphenyl)methanone Chemical compound OC1=CC(O)=CC(C(=O)N2[C@@H](C[C@H](CC2)NCC=2C3=CC=CC=C3N=CC=2)CC=2C=CC=CC=2)=C1 DOXKBIISJMVOAL-BJKOFHAPSA-N 0.000 description 1
- PFTLOBQREFSYPO-IZZNHLLZSA-N [(2r,4s)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-(3,5-dimethoxyphenyl)methanone Chemical compound COC1=CC(OC)=CC(C(=O)N2[C@@H](C[C@H](CC2)NCC=2C3=CC=CC=C3N=CC=2)CC=2C=CC=CC=2)=C1 PFTLOBQREFSYPO-IZZNHLLZSA-N 0.000 description 1
- MWWOEKASVSVWFT-IZZNHLLZSA-N [(2r,4s)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-(3-chlorophenyl)methanone Chemical compound ClC1=CC=CC(C(=O)N2[C@@H](C[C@H](CC2)NCC=2C3=CC=CC=C3N=CC=2)CC=2C=CC=CC=2)=C1 MWWOEKASVSVWFT-IZZNHLLZSA-N 0.000 description 1
- WUYRGUCXBKZRJD-IZZNHLLZSA-N [(2r,4s)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-(4-chlorophenyl)methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)N1[C@H](CC=2C=CC=CC=2)C[C@@H](NCC=2C3=CC=CC=C3N=CC=2)CC1 WUYRGUCXBKZRJD-IZZNHLLZSA-N 0.000 description 1
- BENBCXADYMWEMA-WUFINQPMSA-N [(2r,4s)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-naphthalen-1-ylmethanone Chemical compound C([C@@H]1C[C@H](CCN1C(=O)C=1C2=CC=CC=C2C=CC=1)NCC=1C2=CC=CC=C2N=CC=1)C1=CC=CC=C1 BENBCXADYMWEMA-WUFINQPMSA-N 0.000 description 1
- WGTWUAXSBCFCDA-XZWHSSHBSA-N [(2r,4s)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-naphthalen-2-ylmethanone Chemical compound C([C@@H]1C[C@H](CCN1C(=O)C=1C=C2C=CC=CC2=CC=1)NCC=1C2=CC=CC=C2N=CC=1)C1=CC=CC=C1 WGTWUAXSBCFCDA-XZWHSSHBSA-N 0.000 description 1
- YFLRTMKXRQUBGR-IZZNHLLZSA-N [(2r,4s)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-phenylmethanone Chemical compound C([C@@H]1C[C@H](CCN1C(=O)C=1C=CC=CC=1)NCC=1C2=CC=CC=C2N=CC=1)C1=CC=CC=C1 YFLRTMKXRQUBGR-IZZNHLLZSA-N 0.000 description 1
- BOGOWHBQGVNLOS-DHBRAOIWSA-N [(2s,4s)-2-benzyl-4-(2-phenylethylamino)piperidin-1-yl]-(3,5-dimethylphenyl)methanone;hydrochloride Chemical compound Cl.CC1=CC(C)=CC(C(=O)N2[C@H](C[C@H](CC2)NCCC=2C=CC=CC=2)CC=2C=CC=CC=2)=C1 BOGOWHBQGVNLOS-DHBRAOIWSA-N 0.000 description 1
- WQZUOBIIPDZRJP-NSOVKSMOSA-N [(2s,4s)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidin-1-yl]-(3,5-dimethylphenyl)methanone Chemical compound CC1=CC(C)=CC(C(=O)N2[C@H](C[C@H](CC2)NCC=2C3=CC=CC=C3N=CC=2)CC=2C=CC=CC=2)=C1 WQZUOBIIPDZRJP-NSOVKSMOSA-N 0.000 description 1
- AVAYCNNAMOJZHO-UHFFFAOYSA-N [Na+].[Na+].[O-]B[O-] Chemical compound [Na+].[Na+].[O-]B[O-] AVAYCNNAMOJZHO-UHFFFAOYSA-N 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- PYHXGXCGESYPCW-UHFFFAOYSA-N alpha-phenylbenzeneacetic acid Natural products C=1C=CC=CC=1C(C(=O)O)C1=CC=CC=C1 PYHXGXCGESYPCW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- XLJMAIOERFSOGZ-UHFFFAOYSA-N anhydrous cyanic acid Natural products OC#N XLJMAIOERFSOGZ-UHFFFAOYSA-N 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000005116 aryl carbamoyl group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- 125000004532 benzofuran-3-yl group Chemical group O1C=C(C2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
- 239000012965 benzophenone Substances 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- MNMJYMCZPMVAJT-RRPNLBNLSA-N benzyl (2R,4S)-2-benzyl-4-(quinolin-4-ylmethylamino)piperidine-1-carboxylate Chemical compound N1([C@@H](C[C@H](CC1)NCC=1C2=CC=CC=C2N=CC=1)CC=1C=CC=CC=1)C(=O)OCC1=CC=CC=C1 MNMJYMCZPMVAJT-RRPNLBNLSA-N 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- QSRFYFHZPSGRQX-UHFFFAOYSA-N benzyl(tributyl)azanium Chemical compound CCCC[N+](CCCC)(CCCC)CC1=CC=CC=C1 QSRFYFHZPSGRQX-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229940116229 borneol Drugs 0.000 description 1
- CKDOCTFBFTVPSN-UHFFFAOYSA-N borneol Natural products C1CC2(C)C(C)CC1C2(C)C CKDOCTFBFTVPSN-UHFFFAOYSA-N 0.000 description 1
- MOOAHMCRPCTRLV-UHFFFAOYSA-N boron sodium Chemical compound [B].[Na] MOOAHMCRPCTRLV-UHFFFAOYSA-N 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- RRKTZKIUPZVBMF-IBTVXLQLSA-N brucine Chemical compound O([C@@H]1[C@H]([C@H]2C3)[C@@H]4N(C(C1)=O)C=1C=C(C(=CC=11)OC)OC)CC=C2CN2[C@@H]3[C@]41CC2 RRKTZKIUPZVBMF-IBTVXLQLSA-N 0.000 description 1
- RRKTZKIUPZVBMF-UHFFFAOYSA-N brucine Natural products C1=2C=C(OC)C(OC)=CC=2N(C(C2)=O)C3C(C4C5)C2OCC=C4CN2C5C31CC2 RRKTZKIUPZVBMF-UHFFFAOYSA-N 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- FCYRSDMGOLYDHL-UHFFFAOYSA-N chloromethoxyethane Chemical compound CCOCCl FCYRSDMGOLYDHL-UHFFFAOYSA-N 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 125000006639 cyclohexyl carbonyl group Chemical group 0.000 description 1
- KQWGXHWJMSMDJJ-UHFFFAOYSA-N cyclohexyl isocyanate Chemical compound O=C=NC1CCCCC1 KQWGXHWJMSMDJJ-UHFFFAOYSA-N 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical class OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 1
- YFMGHVQBAINRBB-UHFFFAOYSA-L disodium hydrogen carbonate chloride hydrate Chemical compound C([O-])(O)=O.[Na+].Cl.[OH-].[Na+] YFMGHVQBAINRBB-UHFFFAOYSA-L 0.000 description 1
- DTGKSKDOIYIVQL-UHFFFAOYSA-N dl-isoborneol Natural products C1CC2(C)C(O)CC1C2(C)C DTGKSKDOIYIVQL-UHFFFAOYSA-N 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 229960002179 ephedrine Drugs 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- MAOZEDKYMAXDPS-GOSISDBHSA-N ethyl (3r)-3-(benzylamino)-4-phenylbutanoate Chemical compound C([C@H](CC(=O)OCC)NCC=1C=CC=CC=1)C1=CC=CC=C1 MAOZEDKYMAXDPS-GOSISDBHSA-N 0.000 description 1
- BBVPEOYCQVUHMT-LLVKDONJSA-N ethyl (3r)-3-amino-4-phenylbutanoate Chemical compound CCOC(=O)C[C@H](N)CC1=CC=CC=C1 BBVPEOYCQVUHMT-LLVKDONJSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000005446 heptyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005935 hexyloxycarbonyl group Chemical group 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000005929 isobutyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])OC(*)=O 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 229940116298 l- malic acid Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- GPSDUZXPYCFOSQ-UHFFFAOYSA-N m-toluic acid Chemical compound CC1=CC=CC(C(O)=O)=C1 GPSDUZXPYCFOSQ-UHFFFAOYSA-N 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 150000002736 metal compounds Chemical class 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- CZXGXYBOQYQXQD-UHFFFAOYSA-N methyl benzenesulfonate Chemical class COS(=O)(=O)C1=CC=CC=C1 CZXGXYBOQYQXQD-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- PBMIETCUUSQZCG-UHFFFAOYSA-N n'-cyclohexylmethanediimine Chemical compound N=C=NC1CCCCC1 PBMIETCUUSQZCG-UHFFFAOYSA-N 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- XUBWLWIJCBWNDS-SQTGWKPBSA-N n-[(2r)-1,2-dibenzylpiperidin-4-yl]-2,2,2-trifluoroacetamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@H]1CC=2C=CC=CC=2)C(NC(=O)C(F)(F)F)CCN1CC1=CC=CC=C1 XUBWLWIJCBWNDS-SQTGWKPBSA-N 0.000 description 1
- GHZOGBYFUGFJCP-GFOWMXPYSA-N n-[(2r)-2-benzyl-1-(3,5-dimethylbenzoyl)piperidin-4-yl]-2,2,2-trifluoroacetamide Chemical compound CC1=CC(C)=CC(C(=O)N2[C@@H](CC(CC2)NC(=O)C(F)(F)F)CC=2C=CC=CC=2)=C1 GHZOGBYFUGFJCP-GFOWMXPYSA-N 0.000 description 1
- TVPMJLYGHVNXLV-IZZNHLLZSA-N n-[(2r,4s)-2-benzyl-1-(3,5-dichlorobenzoyl)piperidin-4-yl]-2,2,2-trifluoro-n-(quinolin-4-ylmethyl)acetamide Chemical compound C([C@H]1N(CC[C@@H](C1)N(CC=1C2=CC=CC=C2N=CC=1)C(=O)C(F)(F)F)C(=O)C=1C=C(Cl)C=C(Cl)C=1)C1=CC=CC=C1 TVPMJLYGHVNXLV-IZZNHLLZSA-N 0.000 description 1
- WPBLEVHDCVXLCU-LOSJGSFVSA-N n-[(2r,4s)-2-benzyl-1-(3,5-dichlorobenzoyl)piperidin-4-yl]-2-phenylacetamide Chemical compound ClC1=CC(Cl)=CC(C(=O)N2[C@@H](C[C@H](CC2)NC(=O)CC=2C=CC=CC=2)CC=2C=CC=CC=2)=C1 WPBLEVHDCVXLCU-LOSJGSFVSA-N 0.000 description 1
- IDKSGROGHXKFIS-BJKOFHAPSA-N n-[(2r,4s)-2-benzyl-1-(3,5-dichlorobenzoyl)piperidin-4-yl]quinoline-4-carboxamide Chemical compound ClC1=CC(Cl)=CC(C(=O)N2[C@@H](C[C@H](CC2)NC(=O)C=2C3=CC=CC=C3N=CC=2)CC=2C=CC=CC=2)=C1 IDKSGROGHXKFIS-BJKOFHAPSA-N 0.000 description 1
- FFGKOKFXPMSMLT-UHFFFAOYSA-N n-[1-(3,4-dichlorophenyl)pent-4-en-2-yl]-3,5-dimethylbenzamide Chemical compound CC1=CC(C)=CC(C(=O)NC(CC=C)CC=2C=C(Cl)C(Cl)=CC=2)=C1 FFGKOKFXPMSMLT-UHFFFAOYSA-N 0.000 description 1
- OFXVEARSGYOGBL-UHFFFAOYSA-N n-[1-(4-chlorophenyl)pent-4-en-2-yl]-3,5-dimethylbenzamide Chemical compound CC1=CC(C)=CC(C(=O)NC(CC=C)CC=2C=CC(Cl)=CC=2)=C1 OFXVEARSGYOGBL-UHFFFAOYSA-N 0.000 description 1
- OWEQOZVRQAAQAG-UHFFFAOYSA-N n-[1-(4-chlorophenyl)pent-4-en-2-yl]-n-(ethoxymethyl)-3,5-dimethylbenzamide Chemical compound C=1C(C)=CC(C)=CC=1C(=O)N(COCC)C(CC=C)CC1=CC=C(Cl)C=C1 OWEQOZVRQAAQAG-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- NSNPSJGHTQIXDO-UHFFFAOYSA-N naphthalene-1-carbonyl chloride Chemical compound C1=CC=C2C(C(=O)Cl)=CC=CC2=C1 NSNPSJGHTQIXDO-UHFFFAOYSA-N 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000001148 pentyloxycarbonyl group Chemical group 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
- VLCMRTMCMQJSKM-UHFFFAOYSA-N phenyl-[4-phenyl-8-(trifluoromethyl)quinolin-3-yl]methanone Chemical compound C=1C=CC=CC=1C(=O)C1=CN=C2C(C(F)(F)F)=CC=CC2=C1C1=CC=CC=C1 VLCMRTMCMQJSKM-UHFFFAOYSA-N 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 150000003864 primary ammonium salts Chemical class 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
- BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-UHFFFAOYSA-N 0.000 description 1
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 description 1
- BVQGQPVMVBOTID-UHFFFAOYSA-N quinolin-4-ylmethanamine Chemical compound C1=CC=C2C(CN)=CC=NC2=C1 BVQGQPVMVBOTID-UHFFFAOYSA-N 0.000 description 1
- WPYJKGWLDJECQD-UHFFFAOYSA-N quinoline-2-carbaldehyde Chemical compound C1=CC=CC2=NC(C=O)=CC=C21 WPYJKGWLDJECQD-UHFFFAOYSA-N 0.000 description 1
- RYGIHSLRMNXWCN-UHFFFAOYSA-N quinoline-3-carbaldehyde Chemical compound C1=CC=CC2=CC(C=O)=CN=C21 RYGIHSLRMNXWCN-UHFFFAOYSA-N 0.000 description 1
- ALQUTEKNDPODSS-UHFFFAOYSA-N quinoline-4-carbaldehyde-oxime Natural products C1=CC=C2C(C=NO)=CC=NC2=C1 ALQUTEKNDPODSS-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 108060008037 tachykinin Proteins 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- GNKADUQLWRIJRZ-HUUCEWRRSA-N tert-butyl (2r,4r)-2-benzyl-4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@@H](O)C[C@H]1CC1=CC=CC=C1 GNKADUQLWRIJRZ-HUUCEWRRSA-N 0.000 description 1
- IRDYCXRTVGCLGY-UHFFFAOYSA-N tert-butyl 1,4-dioxa-8-azaspiro[4.5]decane-8-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC21OCCO2 IRDYCXRTVGCLGY-UHFFFAOYSA-N 0.000 description 1
- VISOFNWQMKLXOU-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate;ethene Chemical group C=C.CC(C)(C)OC(=O)N1CCC(=O)CC1 VISOFNWQMKLXOU-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Anesthesiology (AREA)
- Rheumatology (AREA)
- Ophthalmology & Optometry (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyridine Compounds (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FI964117A FI964117L (fi) | 1991-08-12 | 1992-08-10 | Menetelmä uusien 1-asyylipiperidiiniyhdisteiden valmistamiseksi |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH237491 | 1991-08-12 | ||
CH237491 | 1991-08-12 |
Publications (3)
Publication Number | Publication Date |
---|---|
FI923575A0 FI923575A0 (fi) | 1992-08-10 |
FI923575A7 FI923575A7 (fi) | 1993-02-13 |
FI104631B true FI104631B (fi) | 2000-03-15 |
Family
ID=4232283
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
FI923575A FI104631B (fi) | 1991-08-12 | 1992-08-10 | Menetelmä uusien 1-asyyli-2-aralkyyli-4-(alkyyli)-aminopiperidiiniyhdisteiden valmistamiseksi |
Country Status (23)
Families Citing this family (111)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK0560268T3 (da) * | 1992-03-13 | 1995-06-12 | Bio Mega Boehringer Ingelheim | Substituerede pipecolinsyrederivater som HIV-proteasehæmmere |
FR2700472B1 (fr) | 1993-01-19 | 1995-02-17 | Rhone Poulenc Rorer Sa | Association synergisante ayant un effet antagoniste des récepteurs NK1 et NK2. |
KR100238346B1 (ko) * | 1993-04-07 | 2000-03-02 | 오쓰까 아끼히꼬 | 피페리딘 유도체를 유효성분으로 하는 말초혈관확장제 |
US5883098A (en) * | 1993-11-29 | 1999-03-16 | Fujisawa Pharmaceutical Co., Ltd. | Piperazine derivatives |
IL111730A (en) * | 1993-11-29 | 1998-12-06 | Fujisawa Pharmaceutical Co | Piperazine derivatives processes for the preparation thereof and pharmaceutical compositions containing the same |
US5610165A (en) * | 1994-02-17 | 1997-03-11 | Merck & Co., Inc. | N-acylpiperidine tachykinin antagonists |
US5935951A (en) * | 1994-09-30 | 1999-08-10 | Novartis Finance Corporation | 1-acyl-4-aliphatylaminopiperidine compounds |
TW397825B (en) * | 1994-10-14 | 2000-07-11 | Novartis Ag | Aroyl-piperidine derivatives |
FR2728169A1 (fr) | 1994-12-19 | 1996-06-21 | Oreal | Utilisation d'un antagoniste de substance p pour le traitement des prurits et des dysesthesies oculaires ou palpebrales |
FR2728165A1 (fr) | 1994-12-19 | 1996-06-21 | Oreal | Utilisation d'un antagoniste de substance p pour le traitement des rougeurs cutanees d'origine neurogene |
FR2728166A1 (fr) | 1994-12-19 | 1996-06-21 | Oreal | Composition topique contenant un antagoniste de substance p |
ATE178886T1 (de) * | 1995-02-22 | 1999-04-15 | Novartis Erfind Verwalt Gmbh | 1-aryl-2-acylamino-ethan-verbindungen und ihre verwendung als neurokinin- insbesondere als neurokinin-1-antagonisten |
RU2156250C2 (ru) * | 1995-04-24 | 2000-09-20 | Новартис Аг | Производные хромона, способ их получения и фармацевтическая композиция |
US6180647B1 (en) | 1995-07-07 | 2001-01-30 | Pfizer Inc. | Substituted benzolactam compounds as substance P antagonists |
US6288225B1 (en) | 1996-05-09 | 2001-09-11 | Pfizer Inc | Substituted benzolactam compounds as substance P antagonists |
NZ321575A (en) * | 1995-10-30 | 1999-05-28 | Janssen Pharmaceutica Nv | 1-(1,2-disubstituted piperidinyl)-4- substituted piperazine derivatives |
JP2000500465A (ja) * | 1995-11-13 | 2000-01-18 | スミスクライン・ビーチャム・コーポレイション | 血液調節化合物 |
FR2741262B1 (fr) | 1995-11-20 | 1999-03-05 | Oreal | Utilisation d'un antagoniste de tnf-alpha pour le traitement des rougeurs cutanees d'origine neurogene |
TW531537B (en) | 1995-12-27 | 2003-05-11 | Janssen Pharmaceutica Nv | 1-(1,2-disubstituted piperidinyl)-4-substituted piperidine derivatives |
WO1997038991A1 (en) | 1996-04-12 | 1997-10-23 | Janssen Pharmaceutica N.V. | Substituted tetracyclic tetrahydrofuran derivatives |
AU2898297A (en) * | 1996-05-24 | 1998-01-05 | Novartis Ag | Use of substance p antagonists for treating social phobia |
MY132550A (en) * | 1996-08-22 | 2007-10-31 | Novartis Ag | Acylaminoalkenylene-amide derivatives as nk1 and nk2 antogonists |
US6344449B1 (en) * | 1996-09-10 | 2002-02-05 | Dr. Karl Thomae Gmbh | Modified aminoacids, pharmaceuticals containing these compounds and method for their production |
JP2001505881A (ja) * | 1996-12-02 | 2001-05-08 | メルク シヤープ エンド ドーム リミテツド | 精神分裂症疾患を治療するためのnk−1受容体拮抗薬の使用 |
US6100256A (en) * | 1996-12-02 | 2000-08-08 | Merck Sharp & Dohme Ltd. | Use of NK-1 receptors antagonists for treating schizophrenic disorders |
JP2001524960A (ja) * | 1997-04-24 | 2001-12-04 | メルク シヤープ エンド ドーム リミテツド | 摂食障害を治療するためのnk−1受容体拮抗薬の使用 |
GB9716457D0 (en) * | 1997-08-04 | 1997-10-08 | Merck Sharp & Dohme | Therapeutic agents |
CA2298777A1 (en) * | 1997-08-04 | 1999-02-18 | Merck Sharp & Dohme Limited | Use of nk-1 receptor antagonists for treating mania |
WO1999007375A1 (en) * | 1997-08-04 | 1999-02-18 | Merck Sharp & Dohme Limited | Use of nk-1 receptor antagonists for treating aggressive behaviour disorders |
GB9716463D0 (en) * | 1997-08-04 | 1997-10-08 | Merck Sharp & Dohme | Therapeutic agents |
US6319920B1 (en) * | 1998-02-27 | 2001-11-20 | Syntex (U.S.A.) Llc | 2-arylethyl-(piperidin-4-ylmethyl)amine derivatives |
DZ2769A1 (fr) * | 1998-04-17 | 2003-12-01 | Lilly Co Eli | Composés tricycliques substitués. |
TW537894B (en) * | 1998-05-26 | 2003-06-21 | Novartis Ag | A spontaneously dispersible pharmaceutical composition comprising a piperidine substance P antagonist |
FR2780057B1 (fr) * | 1998-06-18 | 2002-09-13 | Sanofi Sa | Phenoxypropanolamines, procede pour leur preparation et compositions pharmaceutiques les contenant |
GB9816897D0 (en) * | 1998-08-04 | 1998-09-30 | Merck Sharp & Dohme | Therapeutic use |
JP4510290B2 (ja) * | 1998-08-25 | 2010-07-21 | ノバルティス アーゲー | 慢性疲労症候群および/または線維筋痛の処置のためのサブスタンスpアンタゴニストの使用および慢性疲労症候群の処置のためのnk−1レセプターアンタゴニストの使用 |
FR2789390B3 (fr) * | 1999-02-10 | 2001-03-09 | Sanofi Sa | Nouveaux derives de piperidine, procede pour leur obtention et compositions pharmaceutiques les contenant |
US6313097B1 (en) | 1999-03-02 | 2001-11-06 | Boehringer Ingelheim Pharma Kg | Antagonists of calcitonin gene-related peptide |
EA004233B1 (ru) * | 1999-05-21 | 2004-02-26 | Пфайзер Продактс Инк. | Производные 1-трифторметил-4-гидрокси-7- пиперидиниламинометилхромана в качестве антагонистов вещества р |
GB9917408D0 (en) * | 1999-07-23 | 1999-09-22 | Smithkline Beecham Plc | Compounds |
GB9917406D0 (en) | 1999-07-23 | 1999-09-22 | Smithkline Beecham Plc | Compounds |
US7163949B1 (en) | 1999-11-03 | 2007-01-16 | Amr Technology, Inc. | 4-phenyl substituted tetrahydroisoquinolines and use thereof |
PT1246806E (pt) | 1999-11-03 | 2008-04-03 | Amr Technology Inc | Tetra-hidroisoquinolinas aril- e heteroaril-substituídas e sua utilização no bloqueio da recaptação de norepinefrina, dopamina e serotonina. |
US7235531B2 (en) | 1999-12-21 | 2007-06-26 | Takeda Pharmaceutical Company | Tachykinin-like polypeptides and use thereof |
EP1299393A2 (en) | 2000-07-11 | 2003-04-09 | Bristol-Myers Squibb Pharma Company | 4-phenyl substituted tetrahydroisoquinolines and therapeutic use thereof |
PL366335A1 (en) | 2000-07-26 | 2005-01-24 | Smithkline Beecham P.L.C. | Aminopiperidine quinolines and their azaisosteric analogues with antibacterial activity |
GB0101577D0 (en) | 2001-01-22 | 2001-03-07 | Smithkline Beecham Plc | Compounds |
WO2002068409A1 (en) | 2001-02-23 | 2002-09-06 | Merck & Co., Inc. | N-substituted nonaryl-heterocyclic nmda/nr2b antagonists |
JP2005511478A (ja) | 2001-04-03 | 2005-04-28 | メルク エンド カムパニー インコーポレーテッド | N−置換非アリール複素環アミジル系nmda/nr2b拮抗薬 |
GB0112836D0 (en) | 2001-05-25 | 2001-07-18 | Smithkline Beecham Plc | Medicaments |
PL370799A1 (en) * | 2001-12-03 | 2005-05-30 | F.Hoffmann-La Roche Ag | Aminotetralin derivatives as muscarinic receptor antagonists |
US7109213B2 (en) * | 2002-01-29 | 2006-09-19 | Glaxo Group Limited | Aminopiperidine compounds, process for their preparation, and pharmaceutical compositions containing them |
EP1470125A1 (en) | 2002-01-29 | 2004-10-27 | Glaxo Group Limited | Aminopiperidine derivatives |
AU2003244455A1 (en) | 2002-02-08 | 2003-09-02 | Glaxo Group Limited | Piperidylcarboxamide derivatives and their use in the treatment of tachykinim-mediated diseases |
GB0203020D0 (en) | 2002-02-08 | 2002-03-27 | Glaxo Group Ltd | Chemical compounds |
TWI283241B (en) * | 2002-05-29 | 2007-07-01 | Tanabe Seiyaku Co | Novel piperidine compound |
RU2294927C2 (ru) * | 2002-05-29 | 2007-03-10 | Танабе Сейяку Ко., Лтд. | Производные пиперидина, способы их получения, фармацевтическая композиция на их основе, их применение и способ лечения |
JP2004285038A (ja) * | 2002-05-31 | 2004-10-14 | Takeda Chem Ind Ltd | ピペリジン誘導体、その製造法および用途 |
TW200409637A (en) | 2002-06-26 | 2004-06-16 | Glaxo Group Ltd | Compounds |
GB0220953D0 (en) * | 2002-09-10 | 2002-10-23 | Novartis Ag | Organic compounds |
ATE354572T1 (de) | 2002-12-23 | 2007-03-15 | Janssen Pharmaceutica Nv | Substituierte 1-piperidin-4-yl-4-azetidin-3-yl- piperazinderivate und deren verwendung als neurokininantagonisten |
JO2485B1 (en) | 2002-12-23 | 2009-01-20 | شركة جانسين فارماسوتيكا ان. في | 1-Piperidine-3-Yl-4-Piperidine-4-Yl-Piperazine derivatives substituted and used as quinine antagonists |
ES2310260T3 (es) | 2002-12-23 | 2009-01-01 | Janssen Pharmaceutica Nv | Derivados sustituidos de 4-(4-piperidin-4-il-piperazin-1-il)-azepan y su uso como antagonistas de la neuroquinina. |
JO2696B1 (en) | 2002-12-23 | 2013-03-03 | شركة جانسين فارماسوتيكا ان. في | Derivatives of 1-piperdine-4-yl-4-biprolidine-3-yl-piperazine substituted and used as quinine antagonists |
US7592360B2 (en) | 2003-06-04 | 2009-09-22 | Merck & Co., Inc. | 3-fluoro-piperidines as NMDA/NR2B antagonists |
KR100877641B1 (ko) * | 2003-11-28 | 2009-01-09 | 미쓰비시 타나베 파마 코퍼레이션 | 피페리딘 화합물 및 그의 제조 방법 |
MY142362A (en) | 2004-01-29 | 2010-11-30 | Otsuka Pharma Co Ltd | Pharmaceutical composition for promoting angiogenesis |
US7232831B2 (en) * | 2004-03-22 | 2007-06-19 | Mediquest Therapeutics, Inc. | Tetrahydro-β-carboline compounds and use thereof |
GEP20094640B (en) | 2004-07-15 | 2009-03-10 | Bristol Myers Squibb Co | Aryl-and heteroaryl-substituted tetrahydro isoquinolines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin |
MX2007011079A (es) | 2005-03-08 | 2007-10-08 | Janssen Pharmaceutica Nv | Derivados de diaza-espiro-[4-4]-nonano como antagonistas de la neurocinina (nk1). |
ES2382814T3 (es) | 2005-05-17 | 2012-06-13 | Merck Sharp & Dohme Ltd. | Ácido cis-4-[(4-clorofenil)sulfonil]-4-(2,5-difluorofenil)ciclohexanopropanoico para el tratamiento del cáncer |
MX2008000717A (es) | 2005-07-15 | 2008-03-18 | Amr Technology Inc | Tetrahidrobenzazepinas substituidas con arilo y heteroarilo y uso de las mismas para bloquear la reabsorcion de norepinefrina, dopamina, y serotonina. |
GB0603041D0 (en) | 2006-02-15 | 2006-03-29 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
GB0607532D0 (en) * | 2006-04-13 | 2006-05-24 | Novartis Ag | Organic compounds |
US20090286790A1 (en) * | 2006-07-20 | 2009-11-19 | Hidetomo Imase | Organic compounds |
US20110218176A1 (en) | 2006-11-01 | 2011-09-08 | Barbara Brooke Jennings-Spring | Compounds, methods, and treatments for abnormal signaling pathways for prenatal and postnatal development |
PL2805945T3 (pl) | 2007-01-10 | 2019-09-30 | Msd Italia S.R.L. | Indazole podstawione grupą amidową jako inhibitory polimerazy poli(adp-rybozy) - (parp) |
AU2008208920A1 (en) | 2007-01-24 | 2008-07-31 | Glaxo Group Limited | Pharmaceutical compositions comprising 3, 5-diamin0-6- (2, 3-dichl0phenyl) -l, 2, 4-triazine or R(-) -2, 4-diamino-5- (2, 3-dichlorophenyl) -6-fluoromethyl pyrimidine and an NK1 |
US8389553B2 (en) | 2007-06-27 | 2013-03-05 | Merck Sharp & Dohme Corp. | 4-carboxybenzylamino derivatives as histone deacetylase inhibitors |
US9156812B2 (en) | 2008-06-04 | 2015-10-13 | Bristol-Myers Squibb Company | Crystalline form of 6-[(4S)-2-methyl-4-(2-naphthyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]pyridazin-3-amine |
AR071997A1 (es) | 2008-06-04 | 2010-07-28 | Bristol Myers Squibb Co | Forma cristalina de 6-((4s)-2-metil-4-(2-naftil)-1,2,3,4-tetrahidroisoquinolin-7-il)piridazin-3-amina |
UA105182C2 (ru) | 2008-07-03 | 2014-04-25 | Ньюрексон, Інк. | Бензоксазины, бензотиазины и родственные соединения, которые имеют ингибирующую nos активность |
SG172382A1 (en) * | 2008-12-23 | 2011-07-28 | Hoffmann La Roche | Dihydropyridone ureas as p2x7 modulators |
US8691825B2 (en) | 2009-04-01 | 2014-04-08 | Merck Sharp & Dohme Corp. | Inhibitors of AKT activity |
AU2010247763B2 (en) | 2009-05-12 | 2015-12-24 | Albany Molecular Research, Inc. | 7-([1,2,4,]triazolo[1,5,-a]pyridin-6-yl)-4-(3,4-dichlorophenyl)-1,2,3,4- tetrahydroisoquinoline and use thereof |
MX2011011900A (es) | 2009-05-12 | 2012-01-20 | Squibb Bristol Myers Co | Formas cristalinas de (s)-7-([1,2,4]triazolo[1,5-a]piridin-6-il)-4 -(3,4-diclorofenil)-1,2,3,4-tetrahidroisoquinolina y usos de las misma. |
ES2446971T3 (es) | 2009-05-12 | 2014-03-11 | Albany Molecular Research, Inc. | Tetrahidroisoquinolinas sustituidas con arilo, heteroarilo, y heterociclo y su uso |
NZ599343A (en) | 2009-10-14 | 2014-05-30 | Merck Sharp & Dohme | Substituted piperidines that increase p53 activity and the uses thereof |
CN103068980B (zh) | 2010-08-02 | 2017-04-05 | 瑟纳治疗公司 | 使用短干扰核酸(siNA)的RNA干扰介导的联蛋白(钙粘蛋白关联蛋白质),β1(CTNNB1)基因表达的抑制 |
KR102072631B1 (ko) | 2010-08-17 | 2020-02-03 | 시르나 쎄러퓨틱스 인코퍼레이티드 | 짧은 간섭 핵산 (siNA)을 사용한 B형 간염 바이러스 (HBV) 유전자 발현의 RNA 간섭 매개 억제 |
EP2608669B1 (en) | 2010-08-23 | 2016-06-22 | Merck Sharp & Dohme Corp. | NOVEL PYRAZOLO[1,5-a]PYRIMIDINE DERIVATIVES AS mTOR INHIBITORS |
EP2613782B1 (en) | 2010-09-01 | 2016-11-02 | Merck Sharp & Dohme Corp. | Indazole derivatives useful as erk inhibitors |
WO2012036997A1 (en) | 2010-09-16 | 2012-03-22 | Schering Corporation | Fused pyrazole derivatives as novel erk inhibitors |
EP3327125B1 (en) | 2010-10-29 | 2020-08-05 | Sirna Therapeutics, Inc. | Rna interference mediated inhibition of gene expression using short interfering nucleic acids (sina) |
EP2654748B1 (en) | 2010-12-21 | 2016-07-27 | Merck Sharp & Dohme Corp. | Indazole derivatives useful as erk inhibitors |
IN2013MN02170A (enrdf_load_stackoverflow) | 2011-04-21 | 2015-06-12 | Piramal Entpr Ltd | |
US9023865B2 (en) | 2011-10-27 | 2015-05-05 | Merck Sharp & Dohme Corp. | Compounds that are ERK inhibitors |
EP3453762B1 (en) | 2012-05-02 | 2021-04-21 | Sirna Therapeutics, Inc. | Short interfering nucleic acid (sina) compositions |
RU2660429C2 (ru) | 2012-09-28 | 2018-07-06 | Мерк Шарп И Доум Корп. | Новые соединения, которые являются ингибиторами erk |
US9655899B2 (en) | 2012-11-28 | 2017-05-23 | Merck Sharp & Dohme Corp. | Compositions and methods for treating cancer |
RU2690663C2 (ru) | 2012-12-20 | 2019-06-05 | Мерк Шарп И Доум Корп. | Замещенные имидазопиридины в качестве ингибиторов hdm2 |
US9540377B2 (en) | 2013-01-30 | 2017-01-10 | Merck Sharp & Dohme Corp. | 2,6,7,8 substituted purines as HDM2 inhibitors |
EP3041938A1 (en) | 2013-09-03 | 2016-07-13 | Moderna Therapeutics, Inc. | Circular polynucleotides |
EP3525785B1 (en) | 2016-10-12 | 2025-08-27 | Merck Sharp & Dohme LLC | Kdm5 inhibitors |
WO2019094311A1 (en) | 2017-11-08 | 2019-05-16 | Merck Sharp & Dohme Corp. | Prmt5 inhibitors |
EP3706747B1 (en) | 2017-11-08 | 2025-09-03 | Merck Sharp & Dohme LLC | Prmt5 inhibitors |
KR20210046009A (ko) | 2018-08-07 | 2021-04-27 | 머크 샤프 앤드 돔 코포레이션 | Prmt5 억제제 |
US11993602B2 (en) | 2018-08-07 | 2024-05-28 | Merck Sharp & Dohme Llc | PRMT5 inhibitors |
WO2020033284A1 (en) | 2018-08-07 | 2020-02-13 | Merck Sharp & Dohme Corp. | Prmt5 inhibitors |
EP4277982A1 (en) * | 2021-01-14 | 2023-11-22 | Alexion Pharmaceuticals, Inc. | Macrocycle complement factor b inhibitors |
JP7728367B2 (ja) | 2021-06-14 | 2025-08-22 | スコーピオン・セラピューティクス・インコーポレイテッド | がんを処置するために使用され得る尿素誘導体 |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1990005525A1 (en) * | 1988-11-23 | 1990-05-31 | Pfizer Inc. | Quinuclidine derivatives as substance p antagonists |
US5145967A (en) * | 1989-04-20 | 1992-09-08 | Anaquest, Inc. | Method for preparing 4-alkoxyalkyl-4-phenylaminopiperdines and derivatives thereof |
IE903957A1 (en) * | 1989-11-06 | 1991-05-08 | Sanofi Sa | Aromatic amine compounds, their method of preparation and¹pharmaceutical compositions in which they are present |
FR2654725B1 (fr) * | 1989-11-23 | 1992-02-14 | Rhone Poulenc Sante | Nouveaux derives de l'isoindolone, leur preparation et les compositions pharmaceutiques qui les contiennent. |
US5126455A (en) * | 1989-12-13 | 1992-06-30 | Glaxo Inc. | Preparation of substituted alkali metal piperidine-4-carboxylates |
PL169187B1 (pl) * | 1990-05-31 | 1996-06-28 | Pfizer | Sposób wytwarzania podstawionych piperydyn PL PL PL |
CA2084193C (en) * | 1990-06-01 | 1998-04-07 | John A. Lowe, Iii | 3-amino-2-aryl quinuclidines |
EP0550635B1 (en) * | 1990-09-28 | 1995-04-19 | Pfizer Inc. | Fused ring analogs of nitrogen containing nonaromatic heterocycles |
-
1992
- 1992-07-27 MY MYPI92001339A patent/MY110227A/en unknown
- 1992-07-30 PH PH44743A patent/PH29963A/en unknown
- 1992-08-01 TW TW081106123A patent/TW204342B/zh not_active IP Right Cessation
- 1992-08-04 AT AT92810594T patent/ATE120456T1/de active
- 1992-08-04 EP EP92810594A patent/EP0532456B1/de not_active Expired - Lifetime
- 1992-08-04 DE DE59201771T patent/DE59201771D1/de not_active Expired - Lifetime
- 1992-08-04 DK DK92810594.9T patent/DK0532456T3/da active
- 1992-08-04 ES ES92810594T patent/ES2070617T3/es not_active Expired - Lifetime
- 1992-08-10 FI FI923575A patent/FI104631B/fi not_active IP Right Cessation
- 1992-08-10 AU AU20965/92A patent/AU660180B2/en not_active Ceased
- 1992-08-10 MX MX9204627A patent/MX9204627A/es unknown
- 1992-08-10 IL IL10276992A patent/IL102769A/en not_active IP Right Cessation
- 1992-08-10 CA CA002075684A patent/CA2075684C/en not_active Expired - Fee Related
- 1992-08-10 NZ NZ243888A patent/NZ243888A/en unknown
- 1992-08-11 US US07/929,186 patent/US5310743A/en not_active Expired - Lifetime
- 1992-08-11 ZA ZA926013A patent/ZA926013B/xx unknown
- 1992-08-11 JP JP04214093A patent/JP3118090B2/ja not_active Expired - Fee Related
- 1992-08-11 RU SU5052784A patent/RU2114829C1/ru active
- 1992-08-11 HU HU9202615A patent/HU221305B1/hu not_active IP Right Cessation
- 1992-08-11 NO NO923123A patent/NO303448B1/no not_active IP Right Cessation
- 1992-08-11 KR KR1019920014407A patent/KR100261367B1/ko not_active Expired - Fee Related
-
1994
- 1994-03-30 SA SA94140632A patent/SA94140632A/ar unknown
- 1994-04-04 US US08/196,360 patent/US5541195A/en not_active Expired - Lifetime
-
1995
- 1995-04-28 GR GR950401075T patent/GR3015954T3/el unknown
- 1995-06-07 US US08/482,704 patent/US5646144A/en not_active Expired - Lifetime
-
1996
- 1996-06-27 IL IL11875096A patent/IL118750A0/xx unknown
-
1997
- 1997-07-04 NO NO973117A patent/NO973117D0/no unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
FI104631B (fi) | Menetelmä uusien 1-asyyli-2-aralkyyli-4-(alkyyli)-aminopiperidiiniyhdisteiden valmistamiseksi | |
EP0930298B1 (en) | Fluorinated 1,4-disubstituted piperidine derivatives | |
EP0820452B1 (en) | Carbonyl-piperazinyl and piperidinil compounds which inhibit farnesyl protein transferase | |
EP1379504B1 (en) | Bipiperidinyl-derivatives and their use as chemokine receptors inhibitors | |
EP0363963B1 (en) | Piperidinyl benzimidazoles as antihistamines | |
EP0277794B1 (en) | N-heterocyclic-N-(4-piperidyl) amides | |
US4680296A (en) | Piperidine derivatives and pharmaceutical compositions containing them | |
US20030105135A1 (en) | Phenoxypropanolamines, preparation and therapeutic use thereof | |
EP0160422A1 (en) | N-Aryl-N-(4-Piperidinyl)amides and pharmaceutical compositions and methods employing such compounds | |
EP0975623B1 (en) | Indazole amide compounds as serotoninergic agents | |
AU2002302511A1 (en) | Bipiperidinyl-derivatives and their use as chemokine receptors inhibitors | |
FI57749C (fi) | Foerfarande foer framstaellning av analgetiska n-/1-(omega-fenylalkyl)-piperidyl-4/-n-(alfa-pyridyl)-karbonsyraamider och deras syraadditionssalter | |
EP0711291B1 (en) | N-(piperidinyl-1-alkyl)-substituted cyclohexane carboxylic acid amides as 5-ht1a receptor antagonists | |
US4912109A (en) | N-heterocyclic-N-(4-piperidinyl) amides and pharmaceutical compositions and methods employing such compounds | |
EP1256575B1 (en) | Phenoxyalkylamine derivatives useful as opioid delta receptor agonists | |
EP0315405A1 (en) | 4-phenyl-4-(N-(2-fluorophenyl)amido) piperidine derivatives | |
US5182399A (en) | Process for preparing piperidinyl benzimidazoles | |
EP1870396B1 (en) | Benzyloxypropylamine derivative | |
US4954506A (en) | N-heterocyclic-N-(4-piperidinyl)amides and pharmaceutical compositions and methods employing such compounds | |
EP0502031B1 (en) | N-substituted azaheterocyclic carboxylic acids and a pharmaceutical composition | |
JPS61161258A (ja) | 1,3,4―三置換アザシクロアルカン及びアザシクロアルケン | |
JPWO2005030722A1 (ja) | N−置換−n−(4−ピペリジニル)アミド誘導体 | |
IE862277L (en) | Hydropyridine derivatives and amino acid intermediates¹thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
GB | Transfer or assigment of application |
Owner name: NOVARTIS AG |
|
MM | Patent lapsed |